Unless you want to waste a large amount of money—often hundreds of dollars a year—by using brand-name instead of generic drugs, you should ask for the generic version, especially if you are starting on a drug for the first time. (See table below.) One of the few bits of comparative information about prescription drugs readily accessible to consumers is the retail price of brand-name versus generic drugs. You can get this information easily by asking your pharmacist. The table below was prepared by simply phoning a local pharmacy.

(2) Prices are average retail prices in brick-and-mortar pharmacies (i.e., chain, independent, and food-store pharmacies, excluding Internet, mail-order, and long-term care pharmacies) across all payer types (cash-only, Medicaid, and other third-party payers) for the first quarter of 2004.

(3) Generic prices are calculated in the same fashion using the median price among generic manufacturers. A weighted average price would have been preferable, but no prescription volume data were available at the time by which to weight the different manufacturers.

(4) Patients using albuterol are assumed to need seven puffs on an average day.

In 1984, generic drugs accounted for less than 19% of all prescriptions filled. Today, generic drugs represent more than 54% of all prescriptions dispensed in the United States. In addition, even though generics account for more than half of prescriptions dispensed, generics account for less than 16 cents of every dollar spent on prescription drugs.2 Today there are more than 7,800 generic versions of the approximately 10,668 FDA-approved pharmaceuticals.3

Brand-name drug manufacturers have gone to extraordinary lengths to mislead doctors, pharmacists, and the public into believing that their products are produced to higher standards, and thus are safer and more effective than the same drugs produced by generic companies. These strategies have included setting up sham patient groups to lobby state legislatures to protect their brand-name drugs, and the suppression of scientific research by at least one brand-name company that showed their brand-name product was no better than those of generic companies.

The quality of prescription drugs, brand-name or generic, does not depend solely on the manufacturer but also on a strong and vigilant FDA. Both brand-name and generic drug companies are regulated by the FDA using the same standards for manufacturing facilities, quality and purity, and content of prescription drugs.

The Question of Brand-Name Quality

Many brand-name drug companies such as Warner-Lambert and its subsidiary, Parke-Davis, denigrate the quality of generic drugs in an attempt to hold market share from generics and protect profits. However, the facts about this brand-name manufacturer bear examining.

From 1990 to the end of 1995, there were a total of 64 recalls of Warner-Lambert products as listed in FDA recall reports. In 1990, there were 3 recalls, 1 in 1991, 3 in 1992, 24 in 1993, 13 in 1994, and 20 in 1995. For their brand of phenytoin (DILANTIN) alone—a drug used primarily for treating seizure disorders and one where the amount of drug in the blood is critical—there have been 12 recalls during this period. Nine of these involved problems with dissolving of the drug, which can result in an insufficient amount being absorbed by the body. More than 975,000 bottles (some of which contained 1,000 capsules) and more than 30,000 injectable doses of Dilantin were affected by these recalls.4

In this case, Warner-Lambert officials pleaded guilty to criminal charges for withholding important information about sloppy manufacturing practices from the FDA.

FDA Repels Attacks on Generic Drugs

As discussed above, it is in the first seven years after approval—when there is never any generic equivalent available because the patent has not yet expired, that most drugs are found to cause serious problems, not infrequently leading to their removal from the market.

Examples of such disasters, which collectively have killed hundreds of Americans and injured thousands more, have involved the arthritis drugs or painkillers Oraflex, Suprol, and Zomax; the antidepressant Merital; the high blood pressure drug Selacryn; the diet drugs Pondimin, one-half of the once popular “fen/phen” combination, and its close chemical cousin Redux; Posicor, a drug for high blood pressure and chest pain; the diabetes drug Rezulin; and the painkiller Duract. Because of the serious dangers of these 10 drugs, all were taken off the market.

But what about those drugs that have been on the market for a long enough time for the patents to have expired and that are available in both brand-name and generic versions? Which version is safer or more effective? It has always been our position that there is no difference between generic and brand-name drugs as far as the odds that there will be something found wrong with the amount of active ingredient or the purity. Over the years, there have been recalls because of these kinds of problems with both generic and brand-name drugs.

A 1990 study by FDA laboratories from all over the country found that for those classes of prescription drugs that theoretically could be most likely to pose safety or effectiveness problems if they were not manufactured properly, the generic drug met the applicable standards in virtually all cases. The classes of drugs tested included contraceptives, antibiotics, and medications prescribed for asthma, epilepsy, high blood pressure, and abnormal heart rhythms. Of the 429 samples of the 24 different drugs tested, including both brand-name and generic drugs, there were no samples tested that posed a health hazard to patients when examined for potency and, where applicable, dissolution rate and content uniformity.

The reason that these 24 different drugs were chosen is that they all have a narrow therapeutic range. This means that unlike with most kinds of drugs, for which there is a relatively large range of dosages that are both effective and relatively safe, the amount of these drugs that gets into the body must be more tightly controlled. If it is not, the drug may too easily lose its effectiveness (if the dose is too low) or become toxic (if the dose is too high).

The drugs that tested included six asthma drugs, four for treating epilepsy, four high blood pressure drugs, four drugs for treating heart arrhythmias, a birth control pill, one antibiotic, a drug for treating depression, and a so-called blood-thinning drug. In six categories of drugs, both brand-name and generic versions were tested. In the case of the birth control pill, all of the major brand names, but no generic version, were tested.

For 23 of the 24 different drugs, there was no difference between the brand-name and the generic versions in the FDA laboratory tests for purity or quality. For aminophylline, an asthma drug that we do not recommend as a first-line treatment, five batches from two manufacturers failed to meet the FDA standards. Although none of these five batches posed a health hazard, all were recalled.5

Listed below are the names, both brand-name and generic, by therapeutic class, of all the drugs studied except for the birth control pill (because no generic version was studied) and aminophylline (AMOLINE, SOMOPHYLLIN, SOMOPHYLLIN-DF). As indicated in the table, many of these manufacturers have changed since the 1990 study because of mergers and acquisitions within the drug industry.

As can be seen in the above table, over the course of a year, for drugs such as the high blood pressure drug lisinopril, which must be taken daily, the savings—365 times $.57 per day—are a hefty $208 in one year; and the savings are hundreds more for others that many people may be using.

Fact: The firm seeking to sell a generic drug must show that its drug delivers the same amount of active ingredient in the same time frame as the original product.

Myth: Generics are not as potent as brand-name drugs.

Fact: FDA requires generics to have the same quality, strength, purity, and stability as brand-name drugs.

Myth: Generics are not as safe as brand-name drugs.

Fact: FDA requires that all drugs be safe and effective and that their benefits outweigh their risks. Since generics use the same active ingredients and are shown to work the same way in the body, they have the same risk-benefit profile as their brand-name counterparts.

Myth: Brand-name drugs are made in modern manufacturing facilities, and generics are often made in substandard facilities.

Fact: The FDA won’t permit drugs to be made in substandard facilities. The FDA conducts about 3,500 inspections a year in all firms to ensure standards are met. Generic firms have facilities comparable to those of brand-name firms. In fact, brand-name firms account for an estimated 50% of generic drug production. They frequently make copies of their own or other brand-name drugs but sell them without the brand name.

Myth: Generic drugs are likely to cause more side effects.

Fact: There is no evidence of this. The FDA monitors reports of adverse drug reactions and has found no difference in the rates between generic and brand-name drugs.

What Is Bioequivalence?

Generics are not required to replicate the extensive clinical trials that have already been used in the development of the original, brand-name drug. These tests usually involve a few hundred to a few thousand patients. Since the safety and efficacy of the brand-name product has already been well established in clinical testing and frequently many years of patient use, it is scientifically unnecessary, and would be unethical, to require that such extensive testing be repeated in human subjects for each generic drug that a firm wishes to market. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent (i.e., performs in the same manner) to the pioneer drug.

One way scientists demonstrate bioequivalence is to measure the time it takes the generic drug to reach the bloodstream and its concentration in the bloodstream in 24 to 36 healthy, normal volunteers. This gives them the rate and extent of absorption—or bioavailability—of the generic drug, which they then compare to that of the pioneer drug. The generic version must deliver the same amount of active ingredients into a patient’s bloodstream in the same amount of time as the pioneer drug.

Using bioequivalence as the basis for approving generic copies of drug products was established by the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act. Brand-name drugs are subject to the same bioequivalency tests as generics when their manufacturers reformulate them.

The FDA has a public obligation to investigate thoroughly all allegations of drug product defects or failures. The agency has not found any of the allegations raised thus far in the brand-name versus generic drug controversy to be valid. The FDA also has an obligation to make known to health care professionals and to the public its conclusions that false or misleading reports are being generated.

The Levothyroxine (SYNTHROID) Scandal

Boots Pharmaceuticals, which became the Knoll Pharmaceutical Company of Mt. Olive, New Jersey, in March 1995, suppressed publication of scientific research for more than two years in order to perpetuate the incorrect public impression that their brand-name version of levothyroxine (SYNTHROID) was more reliable than generic levothyroxine products from three competing companies. The cost to the American public in excessive charges for Synthroid over these two years has been estimated to be $800 million.

Research that contradicted the Boots/Knoll superiority claim was finally published in the April 16, 1997, issue of the Journal of the American Medical Association. It found four generic and brand-name drugs—Synthroid and the three competing levothyroxines—to be bioequivalent by current FDA standards and interchangeable without loss of therapeutic efficacy in the majority of patients for treatment of hypothyroidism (low thyroid).7

Knoll’s predecessor, Boots, contracted with a faculty member and researchers at the University of California at San Francisco (UCSF) in 1987 for a bioequivalence study comparing Synthroid with three competitors’ levothyroxine products. The company paid the researchers $250,000 to do the study. In this case, a finding of bioequivalence would justify the use of less-expensive, equally effective generic products instead of Synthroid. Boots’s expectation was that the study would find Synthroid to be superior to the generics.

The contract contained a clause giving Boots veto power over publication of the study’s results. The problems began in late 1990, when it became known that Synthroid and the other three levothyroxines were the same.

Over the next four years, Boots waged a calculated campaign to discredit the researchers and their work. Once it was clear that the study would not support the claim of Synthroid’s superiority, Boots alleged scores of deficiencies and errors in the study. The university conducted an investigation of how the research was done and found only minor and easily correctable problems. Some members of the investigating panel found Boots’s interactions with the researchers to be “harassment” and characterized the company’s actions as “deceptive and self-serving.” The university concluded that the study was carefully done and complied fully with the terms of the contract.8

The results of the study were submitted to the Journal of the American Medical Association in April 1994. The study was sent to five experts for peer review and was accepted for publication in November 1994, with its publication scheduled for the January 25, 1995, issue of the journal. On January 13, 1995, the researchers suddenly withdrew the study from publication, citing as the reason “impending legal action by Boots Pharmaceuticals, Inc. against UCSF and the investigators.” Because of the clause in the contract giving the company veto power over publication, UCSF said it would not defend the researchers if the study was printed without the company’s permission.8

Then, in a move striking at the very core of ethical scientific standards, the company’s senior director for medical research took the study results and, without giving credit to the UCSF researchers, published a misleading version in an obscure journal of which he was also an associate editor. The new version was used to support the company’s previous assertion of Synthroid’s superior reliability.

Six years after it was known that there was no difference between Synthroid and generic levothyroxine products, and more than two years after the UCSF research should have been published, the Journal of the American Medical Association published the research just as it would have appeared in January 1995, had it not been for Boots’s interference.

To sum it all up, generic drugs are just as effective and safe as brand-name drugs. Unless you want to waste quite a bit of money, ask your pharmacist to fill your prescription with a generic drug. If the brand-name drug is not yet off patent, your pharmacist will advise you of this. See the table on p. 881 for some examples of generic savings.

As is well known, the only reason that United States residents have increasingly turned to the Internet or to Canada as a source for drugs is that drug prices are out of control at home. Drug prices in foreign countries are often half of what they are for identical drugs in the United States. Unlike every other industrialized country, the United States refuses to negotiate drug prices or, as is done in Britain, negotiate a guaranteed profit margin for pharmaceuticals. In fact, we are in many respects going in the opposite direction; the recently passed Medicare prescription drug legislation actually prevents the Medicare program from using its massive purchasing power to negotiate lower drug prices.

Among its billions of pages, the Web contains a minigrowth industry in prescription drug sales. That much of this industry has its sights trained on the United States should be no surprise: Americans use prescription drugs heavily and, thanks to the failure of the government to restrict prices or profits (as is done in most developed countries), we pay more for them.

Some consumers have responded to drug company pricing double standards by hopping a bus and heading north to Canada, but for most people in the United States, this will not be feasible. A trip to your computer terminal, however, puts you instantly in touch with dozens of drug-selling operations, all eager for your business. But can you trust them?

The General Accounting Office (GAO), an investigative branch of Congress, recently conducted a study examining the practices of Internet pharmacy sales. The results should give pause to anyone contemplating succumbing to the allure of the less expensive products on offer on the Web.9

The GAO identified 13 drugs of particular interest and filed orders with 90 different pharmacies around the world; in the end, 68 drugs were received. The top-selling drugs, including Celebrex, Lipitor, and (of course!) Viagra, were generally widely available, but drugs requiring patient monitoring to protect patient safety (Accutane, Clozaril) and narcotic pain relievers (OxyContin, Percocet) were tougher to find.

All six pharmacies that accepted payments for the drug and then failed to fill the order were located outside of the United States or Canada. Not one of the 21 drugs obtained from outside the United States or Canada included a product label and only six contained warning information. Most improperly shipped drugs came from these countries as well: insulin that was not refrigerated, moisture-sensitive drugs that were not sealed, drugs hidden in compact disc cases, and drugs labeled as “dye and stain remover wax.”

But the United States and Canadian sites were certainly not immune from problems. Sixteen of 18 Canadian drugs did not comply with U.S. regulations in that the packaging or labeling had not been approved by the FDA or the agency had not inspected the manufacturing plant. (These drugs may well have met the requirements of Canadian regulatory authorities, and Canadian labeling is quite similar to that in the United States.) However, all 29 U.S. and all 18 Canadian drugs proved to have the proper amount of the active ingredient, while four of the other foreign drugs did not.

Where the United States proved particularly inadequate was in requiring a prescription. Internet pharmacies are usually divided into three groups: (1) those to whom you have to mail a prescription; (2) those that have you fill out a questionnaire online and that, without ever examining you, dispense the drug; and (3) those that don’t even maintain the pretense of a questionnaire and simply provide the drugs. Most states consider the latter two options to constitute an improper practice of medicine but have generally failed to discipline those physicians lending their names to such schemes. Only five of the 29 United States sites required a prescription, with the remainder requiring the online questionnaire. Three of the non-Canadian foreign sites required a questionnaire, but the remaining 18 simply mailed the drugs. In contrast, every Canadian pharmacy required a prescription from the patient’s own physician, the most reputable option.

The United States government, at least, seems to suspect that illegal activity is rife in this industry. Fourteen of the 68 pharmacies (nine United States, one Canadian, and four from other foreign countries) were under investigation by either the United States FDA or the Drug Enforcement Administration for allegations including selling controlled substances without a prescription, lack of a doctor-patient relationship, selling adulterated or counterfeit drugs, smuggling, and mail fraud.

Given the way the drugs were obtained, it is difficult to make general statements about the reliability of different countries’ Internet sites. The most reliable predictor of Web site quality appears to be whether or not it requires a prescription from your own doctor. Ironically, given the current focus on drug importation, the GAO data suggest that, on this measure at least (and assuming you are willing to accept Canadian regulatory standards as equivalent to those in the United States), if you’re going to hop on a virtual Internet bus, it would be best if it were pointed North.

Importing Drugs from Canada

Spiraling drug prices have also driven desperate consumers to look to foreign countries, particularly Canada, to obtain prescription drugs at affordable prices. The FDA and the pharmaceutical industry have complained that such importation is unsafe, due to possible counterfeiting, poor quality manufacturing, and contamination. Counterfeits are a long-standing problem in United States health care, predating the importation debate by decades. The problem is not restricted to imports; domestically manufactured drugs are also all-too-frequently counterfeited or adulterated.

Yet, while the FDA continues to raise concern over counterfeiting, in part by producing misleading reports that exaggerate the problem or focus on the importation dimension of it alone, the agency is in fact part of the problem. A law that was designed to cut down on counterfeiting has, 17 years after it was passed, still not been implemented, thanks to industry-inspired delays at the FDA.

The absurdity of the current situation can be appreciated by analogy. If a car develops a safety problem, the manufacturer has the ability to track down each car from, for example, that model-year to inform the current owner of the problem, no matter how many times the car has been resold. Incredibly, this is not possible for pharmaceuticals.

Historically, the path from a pharmaceutical manufacturer to a consumer was relatively simple: manufacturers sold to wholesalers who sold to hospitals or pharmacists who administered medications or filled prescriptions. Over the years, this path has become circuitous. Secondary wholesalers might obtain the drugs from one of the three major (primary) wholesalers and then sell it to hospitals or pharmacists. Sometimes primary wholesalers obtain drugs from the secondary wholesalers. Occasionally, secondary wholesalers procure the drugs from the manufacturers themselves. These circuitous roots to the patient provide the opportunity for counterfeiters and other fly-by-night operators to insert themselves into the process. In the process, quality assurances may be lost as drugs are not properly stored, for example.

A document could easily circulate with the batch of drugs with each resale, greatly reducing the possibility of counterfeiting or adulteration, because the perpetrator could be more easily identified. Such a document, called a pedigree, was mandated by Congress in the Prescription Drug Marketing Act (PDMA) of 1987. Even the pharmaceutical companies support it, presumably because it would protect their brands from being tarred by counterfeit knock-offs. In 1988, the FDA issued a guidance document that laid out its interpretation of the PDMA. However, the FDA did not even propose a regulation to implement the PDMA until 1994, and a final regulation was not completed until 1999. In fact, the final regulation was very similar to the 1988 guidance. It was only at that point that complaints from the drug wholesaling industry, which claimed that the paperwork would endanger their profitability, began in earnest. Ironically, it is among these very wholesalers that the counterfeiters lurk. Nonetheless, the FDA has “delayed” implementation of the rule five times, most recently through December 2006. Through these accumulating stalling tactics, the FDA has so far succeeded in frustrating the intent of Congress for 17 years.

This important public health issue has thus been in limbo since 1987, with the FDA never implementing its regulations but nonetheless assailing counterfeiters and importers who are aided and abetted by the FDA’s failure to regulate. Meanwhile, the secondary wholesalers practice business as usual—all at the cost of potentially exposing United States patients to counterfeit and adulterated drugs.

This leaves consumers in the lurch. On the one hand, they are besieged by rising drug prices; on the other they have been abandoned by the very agency that is supposed to protect them from counterfeiters. (The increasingly pro-industry FDA apparently is seeking to protect manufacturers’ profits by preventing the importation of less expensive drugs, an ironic stance for an administration that claims affinity to free-market principles.) For now, the best course is to write your congressperson and the FDA demanding that the congressionally mandated pedigree be implemented. If you live close to the Canadian border, a trip north to take advantage of the prices secured by a government that actually protects its residents from the profiteering of the pharmaceutical industry is probably reasonable.